4-oxo-4,5-dihydrothiazole derivative, preparation method and use thereof

Abstract

The present invention relates to a compound represented by Formula I, a racemate or optical isomer thereof, or a pharmaceutically acceptable salt, a solvate or a hydrate thereof, a pharmaceutical composition comprising the compound, and a use thereof in the manufacture of a medicament for preventing and/or treating a disease or disorder associated with a viral infection.

What is claimed is: 
     
       1. A compound represented by Formula Ic or Formula Id, a racemate or an optical isomer thereof, or a pharmaceutically acceptable salt, a solvate or a hydrate thereof 
       
         
           
           
               
               
           
         
         wherein, R 3  represents 1, 2, 3 or 4 identical or different substituents present on the phenyl ring, each R 3  is independently selected from the group consisting of: hydrogen, halogen, hydroxyl, C 1-8  alkyl, C 1-8  haloalkyl, C 1-8  alkoxy, amino, amino monosubstituted or disubstituted with C 1-8  alkyl, carboxyl, R′(C═O)NH—, and phenyl, wherein R′ is C 1-8  alkyl. 
       
     
     
       2. The compound according to  claim 1 , racemate or an optical isomer thereof, or a pharmaceutically acceptable salt, a solvate or a hydrate thereof, wherein, R 3  represents 1, 2, or 3 identical or different substituents present on the phenyl ring, each R 3  is independently selected from the group consisting of: hydrogen, halogen, hydroxyl, C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  alkoxy, amino, amino monosubstituted or disubstituted with C 1-6  alkyl, carboxyl, R′(C═O)NH—, and phenyl, wherein R′ is C 1-6  alkyl. 
     
     
       3. The compound according  claim 1 , a racemate or an optical isomer thereof, or a pharmaceutically acceptable salt, a solvate or a hydrate thereof, which is selected from the group consisting of:
 Naphthalene-1-sulfonic acid (4-oxo-5-phenylamino-4,5-dihydro-thiazol-2-yl) amide (Compound 13), and 
 Naphthalene-1-sulfonic acid {5-[(4-bromo-phenyl)-phenyl-methyl]-4-oxo-4,5-dihydro-thiazol-2-yl} amide (Compound 14). 
 
     
     
       4. A pharmaceutical composition, comprising at least one compound according to  claim 1 , a racemate or an optical isomer thereof, or a pharmaceutically acceptable salt, a solvate or a hydrate thereof, and one or more pharmaceutically acceptable carriers or excipients. 
     
     
       5. A method for treatment of a viral infection caused by EV71, comprising administering to a subject in need thereof a therapeutically effective amount of at least one compound according to  claim 1 , a racemate or an optical isomer thereof, or a pharmaceutically acceptable salt, a solvate or a hydrate thereof. 
     
     
       6. A method for treatment of hand-foot-mouth disease, comprising administering to a subject in need thereof a therapeutically effective amount of at least one compound according to  claim 1 , a racemate or an optical isomer thereof, or a pharmaceutically acceptable salt, a solvate or a hydrate thereof. 
     
     
       7. The compound according to  claim 2 , a racemate or an optical isomer thereof, or a pharmaceutically acceptable salt, a solvate or a hydrate thereof, wherein R 3  represents 1 or 2 identical or different substituents present on the phenyl ring, each R 3  is independently selected from the group consisting of: hydrogen, halogen, hydroxyl, C 1-4  alkyl, C 1-4  haloalkyl, C 1-4  alkoxy, amino, amino monosubstituted or disubstituted with C 1-4  alkyl, carboxyl, R′(C═O)NH—, and phenyl, wherein R′ is C 1-4  alkyl. 
     
     
       8. The compound according to  claim 2 , racemate or an optical isomer thereof, or a pharmaceutically acceptable salt, a solvate or a hydrate thereof, wherein R 3  represents 1 or 2 identical or different substituents present on the phenyl ring, each R 3  is independently selected from the group consisting of: hydrogen, fluorine, chlorine, bromine, hydroxyl, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, trifluoromethyl, methoxy, ethoxy, propoxy, amino, methylamino, dimethylamino, ethylamino, diethylamino, propylamino, carboxyl, CH 3 (C═O)NH—, C 2 H 5 (C═O)NH—, and phenyl. 
     
     
       9. The compound according to  claim 2 , racemate or an optical isomer thereof, or a pharmaceutically acceptable salt, a solvate or a hydrate thereof, wherein R 3  represents 1 or 2 identical or different substituents present on the phenyl ring, each R 3  is independently selected from the group consisting of: hydrogen, fluorine, chlorine, bromine, hydroxyl, methoxy, amino, diethylamino, propylamino, carboxyl, CH 3 (C═O)NH—, and phenyl. 
     
     
       10. A compound, a racemate or an optical isomer thereof, or a pharmaceutically acceptable salt, a solvate or a hydrate thereof, which is selected from the group consisting of:
 Naphthalene-1-sulfonic acid [5-(3-methoxy-4-hydroxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-yl] amide (Compound 2), 
 Naphthalene-1-sulfonic acid [5-(2-hydroxy-4-diethylamino-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-yl] amide (Compound 3), 
 Naphthalene-1-sulfonic acid [5-(4-chloro-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-yl] amide (Compound 4), 
 Naphthalene-1-sulfonic acid [5-(4-carboxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-yl] amide (Compound 5), 
 Naphthalene-1-sulfonic acid [5-(3-hydroxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-yl] amide (Compound 6), 
 Naphthalene-1-sulfonic acid [5-(3-hydroxy-4-methoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-yl] amide (Compound 7), 
 Naphthalene-1-sulfonic acid [5-(3-bromo-4-hydroxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-yl] amide (Compound 8), 
 Naphthalene-1-sulfonic acid [5-(2,6-dimethoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-yl] amide (Compound 9), 
 Naphthalene-1-sulfonic acid [5-(2-chloro-4-fluoro-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-yl] amide (Compound 10), 
 Naphthalene-1-sulfonic acid (5-biphenyl-4-yl-methylene-4-oxo-4,5-dihydro-thiazol-2-yl) amide (Compound 11), and 
 Naphthalene-1-sulfonic acid [5-(4-acetylamino-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-yl] amide (Compound 12). 
 
     
     
       11. A pharmaceutical composition, comprising at least one compound according to  claim 10 , a racemate or an optical isomer thereof, or a pharmaceutically acceptable salt, a solvate or a hydrate thereof, and one or more pharmaceutically acceptable carriers or excipients. 
     
     
       12. A method for treatment of a viral infection caused by EV71, comprising administering to a subject in need thereof a therapeutically effective amount of at least one compound according to  claim 10 , a racemate or an optical isomer thereof, or a pharmaceutically acceptable salt, a solvate or a hydrate thereof. 
     
     
       13. A method for treatment of hand-foot-mouth disease, comprising administering to a subject in need thereof a therapeutically effective amount of at least one compound according to  claim 10 , a racemate or an optical isomer thereof, or a pharmaceutically acceptable salt, a solvate or a hydrate thereof.